This invention relates to novel pharmaceutical combinations comprising cyclo-(N-methyl-Ala-Tyr-D-Trp-Lys-Val-Phe) and one or more non-steroidal anti-inflammatory/analgesic drugs (NSAID) particularly indomethacin, ibuprofen, diclofenac, and naproxen. Unexpectedly, these novel combinations exhibit remarkable ability to prevent gastrointestinal intolerance that is normally associated with NSAIDs. They are therefore superior to the separate NSAIDs in the treatment of chronic rheumatoid arthritis or osteroarthritis.
Non-narcotic analgesics, also known as non-steroidal anti-inflammatory drugs (NSAID), are widely administered orally in the treatment of inflammation and mild to moderate pain. Within this class, the compounds vary widely in their chemical structure and in their biological profiles as analgesics, anti-inflammatory agents and antipyretic agents. Aspirin, acetaminophen and phenacetin have long been among the most commonly used members of this group; more recently, however, a large number of alternative non-narcotic agents offering a variety of advantages over the earlier drugs have been developed. Addiction to these drugs is not generally a problem with their continuous use in the treatment of pain, acute or chronic inflammatory diseases, (notably, rheumatoid arthritis, osteoarthritis, and dysmenorrhea). However, these new drugs generally have a higher potential for adverse side-effects particularly those related to gastric ulcers. Among the newer compounds in the non-narcotic analgesic/ non-steroidal anti-inflammatory group are compounds such as indomethacin (INDOCIN), diflunisal (DOLOBID), zomepirac sodium (ZOMAX), ibuprofen (MOTRIN), naproxen (NAPROSYN), feneprofen (NALFON), piroxicam (FELDENE), flurbiprofen, mefenamic acid (PONSTEL) and sulindac (CLINORIL). See Physician's Desk Reference, 35th edition, 1981, and The Merck Index, 9th edition, Merck & Co., Rahway, N.J. (1976), for information on specific non-steroidal anti-inflammatory agents.
Cyclo-(N-methyl-Ala-Tyr-D-Trp-Lys-Val-Phe) is a known compound being described in U.S. Pat. No. 4,310,518 issued to Roger M. Freidinger et al. on Jan. 12, 1982. The compound is a somatostatin analog having the structural formula (A): ##STR1## wherein Ala represents alanine, Tyr represents L-tyrosine, D-Trp represents D-tryptophan, Lys represents L-lysine, Val represents L-valine, and Phe represents L-phenylalanine. The compound inhibits the release of glucagon, growth hormone and insulin. It may also inhibit the release of gastric acid secretions and is therefore suggested by the patent as useful in the treatment of peptic ulcers.
Accordingly, it is the object of the present invention to provide a novel combination of cyclo-(N-methyl-Ala-Tyr-D-Trp-Lys-Val-Phe) and one or more NSAIDs for use in the treatment of chronic rheumatoid arthritis or osteoarthritis devoid of undesirable gastrointestinal hemmorrhage or lesions normally associated with NSAIDs.
Another object of the invention is to provide pharmaceutical compositions for the administration of these combinations.
Still a further object of this invention is to provide an improved method of treating pain and inflammatory conditions by administering a sufficient amount of the novel combinations in a mammalian species in need of such treatment.